Flow Cytometric immunophenotyping is a sensitive technique for analysis of benign and malignant tumors. We are studying the refinement of this technique and its application to diagnosis and measurement of prognostic markers in different systems. The myelodysplastic syndromes (MDS) are characterized by bi- or trilineage dysplasia. Although diagnostic criteria are well established for MDS, a significant number of patients have blood and bone marrow findings that make diagnosis and classification difficult. Flow cytometric immunophenotyping is an accurate and highly sensitive method for detection of quantitative and qualitative abnormalities in hematopoietic cells. We used flow cytometry to study hematopoietic cell populations in the bone marrow of patients with straightforward MDS. The results were compared to those obtained in a series of patients with aplastic anemia, normal donors and patients with a history of non-myeloid neoplasia in complete remission. We defined the immunophenotypic abnormalities associated with MDS and compared the diagnostic utility of flow cytometry with morphological and cytogenetic evaluations in difficult cases. Although morphology and cytogenetics were adequate for diagnosis in the majority of cases, flow cytometry could detect immunophenotypic abnormalities in cases when combined morphology and cytogenetics were non-diagnostic. We conclude that flow cytometric immunophenotyping may help establish the diagnosis of MDS, especially when morphology and cytogenetics are indeterminate. The laboratory has an ongoing interest in detection of minimal and residual lymphoma. We are using multiparametric approaches to improve the sensitivity of detection of monoclonal B-cell populations, especially in small samples such as CSF. By targeting abnormal patterns of antigen expression (eg CD10, CD5, CD23, FMC7, or abnormal intensity of antigen expression) by neoplastic B-cells in light chain detection, we are attempting to detect very small numbers of neoplastic B-cells among admixed polyclonal B-cells. The laboratory is studying specific Flow Cytometric markers of various lymphoma sub-groups to improve diagnostic accuracy.